Live imaging captures how blood stem cells take root in the body

January 15, 2015, Children's Hospital Boston
Blood stem cell en route to taking root in a zebrafish. Credit: Boston Children's Hospital

A see-through zebrafish and enhanced imaging provide the first direct glimpse of how blood stem cells take root in the body to generate blood. Reporting online in the journal Cell today, researchers in Boston Children's Hospital's Stem Cell Research Program describe a surprisingly dynamic system that offers several clues for improving bone marrow transplants in patients with cancer, severe immune deficiencies and blood disorders, and for helping those transplants "take."

The steps are detailed in an animation narrated by senior investigator Leonard Zon, MD, director of the Stem Cell Research Program (see below).

"The same process occurs during a transplant as occurs in the body naturally," says Zon. "Our direct visualization gives us a series of steps to target, and in theory we can look for drugs that affect every step of that process."

"Stem cell and bone marrow transplants are still very much a black box—cells are introduced into a patient and later on we can measure recovery of their blood system, but what happens in between can't be seen," says Owen Tamplin, PhD, the paper's co-first author. "Now we have a system where we can actually watch that middle step. "

The blood system's origins

It had already been known that blood stem cells bud off from cells in the aorta, then circulate in the body until they find a "niche" where they're prepped for their future job creating blood for the body. For the first time, the researchers reveal how this niche forms, using time-lapse imaging of naturally transparent zebrafish embryos and a genetic trick that tagged the stem cells green.

On arrival in its niche (in the zebrafish, this is in the tail), the newborn blood stem cell attaches itself to the blood vessel wall. There, chemical signals prompt it to squeeze itself through the wall and into a space just outside the blood vessel.

"In that space, a lot of cells begin to interact with it," says Zon. Nearby endothelial (blood-vessel) cells wrap themselves around it: "We think that is the beginning of making a stem cell happy in its niche, like a mother cuddling a baby."

As the stem cell is being "cuddled," it's brought into contact with a nearby stromal or "nurse" cell that helps keep it attached. The stem cell hooks onto the nurse cell tightly, in a process Zon likens to early "attachment" of an infant to its mother.

The "cuddling" was reconstructed from confocal and electron microscopy images of the zebrafish taken during this stage. Through a series of image slices, the researchers were able to reassemble the whole 3D structure—stem cell, cuddling endothelial cells, and stromal cells.

"Nobody's ever visualized live how a stem cell interacts with its niche," says Zon. "This is the first time we get a very high-resolution view of the process."

Eventually, the cuddled stem cell begins dividing. One daughter cell leaves the niche while the other stays. Eventually, all the stem cells leave and begin colonizing their future site of blood production (in fish, this is in the kidney).

Further imaging done in mice found evidence that blood stem cells go through much the same process in mammals, which makes it likely in humans too. In humans, set up permanent residence in the bone marrow.

These detailed observations are already informing the Zon Lab's attempt to improve bone marrow transplantation. By doing a chemical screen in large numbers of zebrafish embryos, the researchers found that the compound lycorine promotes interaction between the blood stem cell and its niche, leading to greater numbers of blood in the adult fish.

Explore further: Boning up: Researchers find home of best stem cells for bone marrow transplants

Related Stories

Immune cells regulate blood stem cells

February 21, 2014

Researchers in Bern, Germany, have discovered that, during a viral infection, immune cells control the blood stem cells in the bone marrow and therefore also the body's own defences. The findings could allow for new forms ...

Opening-up the stem cell niche

July 11, 2014

For many years scientists have been trying to unravel mechanisms that guide function and differentiation of blood stem cells, those cells that generate all blood cells including our immune system. The study of human blood ...

KIT researchers develop artificial bone marrow

January 10, 2014

Artificial bone marrow may be used to reproduce hematopoietic stem cells. A prototype has now been developed by scientists of KIT, the Max Planck Institute for Intelligent Systems, Stuttgart, and Tübingen University. The ...

Recommended for you

Research offers new insights into malaria parasite

May 18, 2018

A team of researchers led by a University of California, Riverside, scientist has found that various stages of the development of human malaria parasites, including stages involved in malaria transmission, are linked to epigenetic ...

What we've learned about the nucleolus since you left school

May 17, 2018

The size of a cell's nucleolus may reveal how long that cell, or even the organism that cell belongs to, will live. Over the past few years, researchers have been piecing together an unexpected link between aging and an organelle ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.